Investigation of the molecular and cellular mechanisms of in vitro phage therapy in human cells and of the innate immune response against E. coli O18

抗生素耐药性问题是当今的主要问题，并且显然需要确定抗生素的替代方法来解决细菌病原体。潜在的替代方案之一是噬菌体疗法，即使用对靶向病原体具有高度特异性的噬菌体作为抗微生物剂。尽管最近由于抗微生物剂抗性的问题而对噬菌体治疗的兴趣有所增长，但由于在细菌裂解时免疫应答和快速毒素释放的潜力，仍然存在对这种方法的担忧。在这个项目中，我们的目标是研究体外噬菌体治疗的细胞机制，使用受感染的人类细胞系模型模拟由感兴趣的病原体引起的疾病，并进一步确定测量人类细胞环境中针对靶向病原体和噬菌体的先天免疫应答的方法。此外，我们将构建与野生型相比具有优化特征的不同抗体，以用于人细胞环境中，并且我们将比较使用不同条件和不同抗体的免疫应答。我们的目的是调查的条件下，对疟疾的免疫反应是最小的。这些结果将有助于我们更好地研究噬菌体治疗的基本机制以及如何使其更安全。

The problem of antimicrobial resistance is nowadays major and the need to identify alternative methods to antibiotics to tackle bacterial pathogens is obvious. One of the potential alternatives is phage therapy, the use of bacteriophages with high specificity against the targeted pathogen, as antimicrobial agents. Even though the interest in phage therapy has grown lately due to the problem of antimicrobial resistance, there are still concerns of this approach among others because of the potential for immune responses and rapid toxin release upon bacterial lysis. In this project, we aim to investigate the cellular mechanisms of phage therapy in vitro, using infected human cell line models mimicking the disease caused by the pathogen of interest, and further identify ways to measure the innate immune response in human cell environment against the targeted pathogen and the phage. Additionally, we will construct different phages with optimized characteristics compared to the wild type to be used in human cell environment and we will compare the immune response using different conditions and the different phages. Our aim is to investigate the conditions in which the immune response against phages is minimal. These results will help us investigate better the basic mechanisms of phage therapy and how it can be made safer.